Experimental and Clinical Research Center (a Joint Institution Between the Charité University Medicine and Max Delbrück Center for Molecular Medicine), Berlin-Buch, Germany; and Nephrology/Intensive Care Section, Charité Campus Virchow, Berlin, Germany
Experimental and Clinical Research Center (a Joint Institution Between the Charité University Medicine and Max Delbrück Center for Molecular Medicine), Berlin-Buch, Germany; and Nephrology/Intensive Care Section, Charité Campus Virchow, Berlin, Germany.
Am J Physiol Heart Circ Physiol. 2014 Sep 15;307(6):H811-7. doi: 10.1152/ajpheart.00319.2014. Epub 2014 Jul 11.
Over the last decades, cardiovascular disease has become the primary cause of death in the Western world, and this trend is expanding throughout the world. In particular, atherosclerosis and the subsequent vessel obliterations are the primary cause of ischemic disease (stroke and coronary heart disease). Excess calcium influx into the cells is one of the major pathophysiological mechanisms important for ischemic injury in the brain and heart in humans. The large-conductance calcium-activated K(+) channels (BK) are thus interesting candidates to protect against excess calcium influx and the events leading to ischemic injury. Indeed, the mitochondrial BK channels (mitoBK) have recently been shown to play a protective function against ischemia-reperfusion injury both in vitro and in animal models, although the exact mechanism of this protection is still under scrutiny. In addition, in both the plasma membrane and mitochondrial BK channel, the α-subunit itself is sensitive to hypoxia. This sensitivity is tissue specific and conferred by a highly conserved motif within an alternatively spliced cysteine-rich insert (STREX) in the intracellular C terminus of the channel. This review describes recent developments of the increasing relevance of BK channels in hypoxia and ischemia-reperfusion injury.
在过去几十年中，心血管疾病已成为西方世界的主要死亡原因，而且这种趋势正在全球范围内蔓延。特别是动脉粥样硬化和随后的血管闭塞是缺血性疾病（中风和冠心病）的主要原因。细胞内钙离子内流过多是人类脑和心脏缺血损伤的主要病理生理机制之一。大电导钙激活钾（BK）通道因此成为防止过度钙离子内流和导致缺血损伤的有趣候选者。事实上，线粒体 BK 通道（mitoBK）最近已被证明在体外和动物模型中具有对抗缺血再灌注损伤的保护作用，尽管这种保护的确切机制仍在研究之中。此外，在质膜和线粒体 BK 通道中，α亚基本身对缺氧敏感。这种敏感性是组织特异性的，由通道细胞内 C 末端的一个高度保守的、选择性剪接的富含半胱氨酸插入（STREX）中的一个模体赋予。本文综述了 BK 通道在缺氧和缺血再灌注损伤中日益重要的最新研究进展。
